Clusterin inhibition using OGX-011 synergistically enhances antitumour activity of sorafenib in a human renal cell carcinoma model.

British Journal of Cancer
Y KususdaM Fujisawa

Abstract

The objective of this study was to investigate whether the therapeutic activity of sorafenib could be enhanced by combining with OGX-011, an antisense oligodeoxynucleotide (ODN) targeting clusterin, in renal cell carcinoma (RCC). We investigated the effects of combined treatment with OGX-011 and sorafenib on a human RCC ACHN model both in vitro and in vivo. Although clusterin expression was increased by sorafenib, additional treatment of ACHN with OGX-011 significantly blocked the upregulation of clusterin induced by sorafenib. Despite the lack of a significant effect on the growth of ACHN, OGX-011 synergistically enhanced the sensitivity to sorafenib, reducing the IC(50) by >50%. Apoptotic changes were intensively detected in ACHN after combined treatment with OGX-011 and a sublethal dose of sorafenib, but not either agent alone. Furthermore, this combined treatment resulted in the marked downregulation of phosphorylated Akt and p44/42 mitogen-activated protein kinase in ACHN compared with treatment with either agent alone. In vivo systemic administration of OGX-011 plus sorafenib significantly decreased the ACHN tumour volume compared with control ODN plus sorafenib. Combined use with OGX-011 may be useful in enhancing the cy...Continue Reading

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Citations

Dec 21, 2013·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·K HaradaM Fujisawa
May 5, 2017·Anti-cancer Drugs·Marilina García-ArandaMaximino Redondo
Oct 8, 2013·Reviews in Endocrine & Metabolic Disorders·S ParkI K Lee
Oct 2, 2019·Cancer Medicine·Liwen RenGuanhua Du
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Jan 2, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Prakash Priyadarshi PraharajSujit Kumar Bhutia
Jun 18, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yu HeShufang Liang
Jul 23, 2021·Journal of Chemotherapy·Mandeep Dahiya, Harish Dureja

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Methods Mentioned

BETA
fluorescence microscopy
ELISA
electrophoresis

Software Mentioned

Statview
Basic Local Alignment Search Tool

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